PROJECT SUMMARY Cannabis is the most commonly used drug by women during pregnancy with an estimated prevalence of use in Colorado of 5.7%. THC and its metabolites freely cross the placenta and blood-brain barrier to bind with cannabinoid receptors, disrupting the endogenous cannabinoid signaling system during a critical period of development of cortical circuitry structure and function. The density of cannabinoid receptors in the developing brain is high, especially in the limbic areas and prefrontal lobes. Research in animal models suggests synaptic plasticity in the prefrontal lobes as well the amygdala and hippocampus are impacted by the prenatal cannabis exposure; regions associated with both cognitive and emotional control, thus influencing long- term deficiencies in attention and impulsivity. The premise of our pilot project is to collect preliminary data on the structural impact of in utero cannabis exposure on region-specific morphology and structural connectivity of white matter tracts that connect to the prefrontal lobes and the limbic regions shortly after birth, before confounding by the postnatal environment becomes a major influence. The overall objective of this project is to evaluate whether in utero exposure to maternal chronic cannabis during pregnancy influences neonatal brain morphology in the prefrontal lobe and its structural connectivity to limbic regions. Structural Imaging studies of the neonatal brain shortly after birth offer an innovative investigative approach to understanding the origins of late-manifesting cognitive and behavioral regulation deficits associated with prenatal cannabis exposure.